Down syndrome is a genetic condition in which a person has 47 chromosomes instead of the usual 46. In most cases, Down syndrome occurs when there is an extra copy of chromosome 21. This form of Down syndrome is known as trisomy 21.
Trisomy 21 is associated with a specific phenotype, which includes a flat profile. This observation is part of Langdon Down's original description of what later became known as Down syndrome. Several radiological studies have reported underdevelopment of the upper jaw, delayed dental growth, reduction in the number and size of teeth, and absence or hypoplasia of the nasal bone in individuals with trisomy 21. See, for example, Farkas et al, “Surface anatomy of the face in Down's syndrome: linear and angular measurements in the craniofacial regions,” J Craniofac Surg, 12:373-9 (2001); Allanson et al, “Anthropometric craniofacial pattern profiles in Down syndrome,” Am J Med Genet, 47:748-52 (1993); impaction in individuals with Down syndrome,” Orthod, 70:290-6 (2000); Mestrovic et al, “Hypodontia in patients with Down's syndrome,” Coll Antropol, 22:69-72 (1998); Kumasaka et al, “Oligodontia: a radiographic comparison of subjects with Down syndrome and normal subjects,” Spec Care Dentist, 17:137-41 (1997); and Russell et al, “Tooth agenesis in Down syndrome,” Am J Med Genet, 55:466-71 (1995).
Furthermore, prenatal sonographic studies have reported that a significant proportion of fetuses with trisomy 21 have shortening of the maxillary length and maxillary depth. See, for example, Cicero et al, “Maxillary length at 11-14 weeks of gestation in fetuses with trisomy 21,” Ultrasound Obstet Gynecol, 24:19-22 (2004); Dagklis et al, “Three-dimensional evaluation of mid-facial hypoplasia in fetuses with trisomy 21 at 11-13+6 weeks,” Ultrasound Obstet Gynecol, 28(3): 261-5 (September 2006); and Berganni et al, “Mid-facial anthropometry in second-trimester fetuses with trisomy 21: a three dimensional ultrasound study,” Prenatal Diagnosis, 26:158-162 (2006). However, from these studies, the reported differences between maxillary measurements between trisomy 21 and euploid fetuses have not been shown to be large enough to be clinically useful. For example, Cicero et al describe a 2D sonographic study at 11-13+6 weeks which showed that trisomy 21 fetuses had a significantly shorter maxillary length as compared to normal. It is below the 5th percentile of the normal range in 24% of affected fetuses. However, the degree of deviation from normal is too small (mean of 0.7 mm) for this measurement to be useful in screening for trisomy 21. Similarly, Dagklis et al describe a 3D sonographic study at 11-13+6 weeks showing that in trisomy 21 fetuses the maxillary depth is shorter than normal by a mean of only 0.3 mm and it is below the 5th percentile of the normal range in only 10% of affected fetuses.